The addition of neoadjuvant chemotherapy to D2 surgery plus adjuvant chemotherapy improves progression-free survival in patients with resectable locally advanced gastric cancer.
The standard of care for patients with locally advanced gastric cancer varies worldwide. In Europe, perioperative chemotherapy with epirubicin plus cisplatin plus fluorouracil is the standard of care. In North America, the standard of care is postoperative chemoradiation, and in Eastern Asia postoperative S-1 or capecitabine plus oxaliplatin is the standard of care. These regimens are based on clinical trials, but treatment improvements are continuously sought mainly by intensifying chemotherapy or modifying adjuvant therapies. The FLOT4, JACCRO GC-07, and ARTIST 2 clinical trials demonstrated that chemotherapy intensification administered postoperatively benefits patients.
The PRODIGY clinical trial, a phase 3 study of neoadjuvant docetaxel, oxaliplatin, and S-1 followed by surgery and adjuvant S-1 (CSC), was performed to determine if this regimen could improve outcomes compared with surgery and adjuvant S-1 (SC) in Korean patients with resectable advanced gastric cancer. There were 693 patients recruited for the study, with 484 patients ultimately undergoing study treatment. Patients ranged between 20 and 75 years of age and had newly confirmed primary locally advanced gastric or gastroesophageal junction adenocarcinoma amenable to surgery. The study’s primary objective was to compare progression-free survival (PFS) between the 2 patient groups. Secondary outcomes included comparison of overall survival (OS), postoperative pathologic stage, R0 resection rate, and safety.
Random assignment (1:1) to a treatment group was made and stratified by site and clinical TNM staging. Within 7 days of random assignment, the CSC group began neoadjuvant treatment of 50 mg/m2 docetaxel and 100 mg/m2 oxaliplatin intravenously on day 1. Oral S-1 at 40 mg/m2 was given twice a day on days 1 through 14 every 3 weeks for 3 cycles. A complete blood count was performed at cycle start and doses were modified, or cycles were delayed if necessary. D2 gastrectomy was performed 1 to 3 weeks after neoadjuvant chemotherapy. The SC group had D2 gastrectomy within 2 weeks of random assignment. Both treatment groups received oral 40- to 60-mg S-1 twice a day on days 1 through 28 every 6 weeks for 8 cycles.
PFS was significantly superior in the CSC arm, with a 3-year PFS rate of 66.3%, compared with 60.2% for the SC arm. OS was consistent for both groups. The 3-year OS was 74.2% for the CSC arm and 73.4% for the SC group. Postoperative pathology in patients who underwent surgery revealed the CSC group had a pathologic complete response rate of 10.4%. Analysis of adverse events (AEs) after adjuvant therapy found that the most common grade ≥3 AE was neutropenia, which occurred in 6.4% of the CSC group and 5.3% of the SC group.
Perioperative docetaxel, oxaliplatin, and S-1 proved to be effective in the patients in this clinical trial.
Source: Kang YK, Yook JH, Park YK, et al. PRODIGY: a phase 3 study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer. J Clin Oncol. 2021;39:2903-2913.